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Toxicologic Pathology
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Web Watch

Mouse Genome Informatics (MGI) Resources for Pathology and Toxicology

Janan T. Eppig, Judith A. Blake, Carol J. Bult, Joel E. Richardson, James A. Kadin, Martin Ringwald and the MGI staff

The Jackson Laboratory Bar Harbor, ME 04609, USA


    Introduction To MGI
 TOP
 Introduction To MGI
 
The Mouse Genome Informatics (MGI, <http://www.informatics.jax.org>) web site supports the use of mouse as a model system. Of particular interest to toxicologists and pathologists are detailed descriptions of phenotypes for mice carrying mutations on specific genetic backgrounds, the human diseases for which these mice are models, information on the incidence and frequency of tumors in inbred and genetically engineered mice, and core data on gene characterization, gene function, and gene expression. Images of gene expression, phenotypes, and tumors (with diagnoses) are also provided.

There are many ways to access MGI data. First, each web page includes a quick Search Box where a word or partial word is entered and the type of data to be searched is specified. Second, query forms allow users to ask complex questions that involve multiple parameters and multiple types of data. Third, MGI generates specific data files for download and analysis. Integrated searches are enabled through use of structured vocabularies (ontologies) for anatomy, gene function (GO), phenotypes, tumor names, and disease terms; and by adherence to international nomenclature standards.

Data in MGI are updated continuously through semiautomated loads, curation of the primary scientific literature, and data submissions from the scientific community. All MGI resources described below are accessible from <http://www.informatics.jax.org>.

Mouse Tumor Biology Database (MTB)
<http://tumor.informatics.jax.org/>

MTB is designed to facilitate selection of experimental models for cancer research, evaluation of mouse genetic models of human cancer, review of patterns of mutations in specific cancers, and identification of genes commonly mutated across a spectrum of cancers. MTB includes data on the organ and tissue of tumor origin, tumor classification, induction treatment, metastases, mouse strains, and specific genes or mutations in the host strain or somatic changes in the tumor.

MTB incorporates data from many laboratories that collect, image and diagnose mouse tumors. The Mouse Pathology Submission interface <http://tumor.informatics.jax.org/mtbpathwi/index.do> allows contributors to create records, specify strain and genetic mutations; generate tumor diagnoses including pathology and treatment descriptions; attach images to diagnoses; and edit and review their submitted data.

The Mouse Tumor Frequency Grid is a visualization tool providing an overview of tumor frequencies and tumor types in different mouse strains <http://tumor.informatics.jax.org/mtbwi/tumorFrequencyGrid.do>. This interactive Grid displays strains on the vertical axis and organs on the horizontal axis. Color-coded cells in the Grid represent tumor frequencies. Each colored cell is an active link, generating a database query for the underlying data. Users can expand the Grid axes for individual strain families and organ systems, thus "zooming-in" on specific sub-strains and tissues of interest.

Mouse Genome Database (MGD)
<http://www.informatics.jax.org>

MGD, the internationally recognized community database for mouse, integrates core data about the genetics, genomics, and biology of the laboratory mouse. Users most frequently begin exploring MGD through their gene of interest. A gene’s Detail Page provides a roadmap, with summary information and many links to deeper detail, including a genetic map, sequence map, orthologs with other species, nucleotide and protein sequences, phenotype summaries, SNPs, gene function (GO), gene expression (GXD links), protein domains, molecular reagents, and references annotated to the gene.

The Phenotype Query form <http://www.informatics.jax.org/searches/alleleform.shtml> can be used to simultaneously search for one or more phenotype terms, e.g., "aortic aneurysm AND emphysema," and users can specify mutation types, e.g., targeted (knock-out), and genes or genome location of interest. An additional tool for phenotype searching is the Mammalian Phenotype Ontology browser <http://www.informatics.jax.org/searches/MP_form.shtml> where phenotype terms are viewed hierarchically from general, e.g., renal/urinary system phenotype to specific, e.g., glomerulonephritis. Each term is directly linked to all mutants annotated to that phenotype. Detail pages for mutant alleles provide extensive phenotype information, data on the mutation itself, disease model information, links to IMSR (see below), and relevant images, including whole mouse photos, histological sections, X-ray, etc.

Users also can search for human disease models in concert with phenotype terms using the Phenotype Query form. In addition, a Human Disease vocabulary (derived from OMIM, Online Mendelian Inheritance in Man) allows one to search for diseases and discover mouse models that have been used in studies of that disease <http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=omimVocab&subset=A>). Links are provided to the OMIM human disease records and to the mouse phenotype descriptions for the model.

Gene Expression Database (GXD)
<http://www.informatics.jax.org/menus/expression_menu.shtml>

GXD stores and integrates different types of expression data for mouse and makes data available in formats appropriate for comprehensive analysis. Emphasis is on endogenous expression during development. GXD describes expression patterns using a hierarchically structured dictionary of anatomical terms. Thus, results from assays with differing spatial resolution are standardized and integrated; and expression patterns can be queried at different levels of detail. Records are complemented with images of original expression data. Data are acquired through literature curation and via electronic submission using a laboratory management tool we have developed, the Gene Expression Notebook (GEN, <http://www.informatics.jax.org/mgihome/GXD/GEN/>), implemented in Microsoft Excel.

Expression data can be searched in multiple ways. The Gene Expression Literature Index can be used as a quick entree into the published literature via gene, ages analyzed, and assay types used. Detailed Gene Expression Data can be searched using parameters such as assay type (RNA in situ, Northern blot, RT-PCR, immunohistochemistry, etc.), genes, ages assayed, mutants, and gene function. An expanded Gene Expression Query form allows one to specify genes expressed in some structures or at some developmental stages, but not others. A vocabulary browser is available for exploring and searching for data using the Mouse Anatomical Dictionary <http://www.informatics.jax.org/searches/anatdict_form.shtml>.

International Mouse Strain Resource (IMSR)
<http://www.imsr.org>

IMSR is a searchable online database of mouse strains and stocks available worldwide, including inbred, mutant, and genetically engineered mice. The goal of the IMSR is to assist the international scientific community in locating and obtaining mouse resources for research. For each strain listed in the IMSR, users can access information about where the strain is available from (repository holder), in what state the strain is available (live, frozen embryo, frozen germplasm, ES cell line), link to descriptive information about the strain, link to data in MGD describing phenotypes of any mutations carried by the strain, and link to a form for contacting the strain holder to order the strain or ask for additional information. The reciprocal links between MGD phenotype records and IMSR strain holder information allow users to approach finding the mice they need from a gene/strain perspective or phenotype perspective.

Toxicologic Pathology, Vol. 35, No. 3, 456-457 (2007)
DOI: 10.1080/01926230701310536


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